治疗性单克隆抗体研究的新趋势兔源单克隆抗体

Rabbit monoclonal antibodies: a novel trend of research of therapeutic antibodies

治疗性抗体正在成为新药开发的新亮点,这些都得益于它可特异的识别靶位。众所周知,目前常用的单克隆抗体多为鼠源,在临床应用方面受到多种限制。与之相比,由于兔的免疫系统自身的特点,兔源单克隆抗体(RabMAbs)具有更高的亲和力和特异性,能识别更多的抗原表位。RabMAbs已在生命科学研究领域中广泛应用,其作为生物标志物已应用到临床诊断和新药研发之中。随着谱系引导的人源化改变(mutational lineage-guided humanization)理论提出和进一步深入研究,使得RabMAbs的人源化不但相对容易还可以对抗原互补决定区与框架区进行人源化。因此,有理由相信治疗性RabMAbs的开发和应用前景更为广阔。文中就RabMAbs的特点、优势、诊断和治疗性RabMAbs的发展状况做一综述。

Therapeutic antibodies are becoming a major focus in development of novel drugs due to their high specificity and affinity to the targets.Mouse-derived monoclonal antibodies（mAbs） are the most commonly used for scientific research and therapeutic treatment.However,the low diversity limited their further development.Recently,antibodies from rabbits are found to have a higher binding affinity and specificity,also a higher ability to recognize novel epitopes.Thus hundreds of RabMAbs are used as reagents to study the biological functions of various proteins.They are also used as biomarkers to evaluate the clinical candidates and their performances in clinical trials.With the theory of mutational lineage-guided（MLG） humanization put forward,humanized RabMAbs are not only relatively straightforward,but also can humanize some residues in the CDRs as the framework do.Taken together,RabMAbs have increased the opportunities for the development of antibody therapeutics.This article reviewed the advantages of RabMAbs and the recent progresses of in vitro diagnostics and humanization.